It is well known that the incidence of mitral valve prolapse is increased in various hereditary and humoral disorders, particularly in diseases with abnormal collagene structure and metabolism. We consecutively investigated, both clinically and echocardiographically, 22 patients with Klinefelter's syndrome (Mean age: 35 +/- 15.8 years). On clinical examination one third (7 patients) showed clinical signs of connective tissue weakness, 9 patients were obese. In 3 patients without a history of rheumatic fever mitral regurgitation was present. A mid-systolic click was heard in 12 patients, in 8 of them a click-murmur syndrome. Mitral regurgitation has been found in 3 patients. Echocardiographic ally, 12 of 22 patients (55%) revealed mitral valve prolapse which was not correlated with the degree of the chromosomal aberration. The incidence of mitral valve prolapse in an otherwise healthy male population is reported to be approximately 6%. Thus, in Klinefelter's syndrome, the frequency of mitral valve prolapse is found to be markedly increased. Regarding the nosological implications of mitral valve prolapse, it is recommended to thoroughly examine patients cardiologically. Furthermore, since mitral valve prolapse bears a higher risk of malignant cardiac arrhythmias, chest pain and endocarditis, an antiarrhythmic treatment and--if indicated--antibiotic prophylaxis has to be instituted. Those patients also should be advised to adjust their life style appropriately.